The proposed research is intended to develop a technique for modification of the tooth surface to prevent or control bacterial colonization (i.e., dental plaque formation). The technique proposed for tooth surface modification is covalent coupling of antibacterial agents to high molecular weight, organic carrier molecules that can be adsorbed or bonded onto tooth surfaces (i.e., analogous to the naturally occurring acquired pellicle). The first specific aim of the proposed research will be to prepare a series of systems that combines by covalent interaction several antibacterial agents with high molecular weight carrier molecules. These systems will include ampicillin coupled to dextran, ampicillin coupled to polyacrylamide, ampicillin coupled to a silane derivative, chlorhexidine coupled to dextran, polymyxin B coupled to dextran or poly-D-glutamate, vancomycin coupled to dextran, oleylamine hydrofluoride coupled to dextran and lysozyme coupled to dextran. The second specific aim will be to test for successful covalent coupling of the antibacterial agents to the carrier molecules. The third specific aim will be to test the covalent combinations of antibacterial agent coupled to carrier molecule for inhibition of bacterial growth. The fourth specific aim will be to evaluate the placement of the carrier molecule onto hydroxyapatite (HA) surfaces (e.g., HA powder or extracted, human teeth) by adsorption or covalent bonding and to determine whether it is better to place the covalent combination on the HA surfaces (i.e., prefabrication) or to place the carrier molecule onto the HA surface followed by coupling of the antibacterial agent (i.e., surface generation). Finally, the fifth specific aim will be to test any combination that inhibits bacterial colonization of HA surfaces. The importance of the work is that it may establish a new approach to preventing bacterial colonization of teeth. Successful completion of this work will demonstrate that antibacterial agents, covalently coupled to tooth-associated, carrier molecules can be effective in preventing in vitro bacterial growth and can be placed on HA surfaces for their ability to prevent in vitro bacterial colonization of teeth. Such a finding will have important implications for preventing dental plaque formation in humans because this concept may provide a unique tool for the dentist to prevent dental caries and periodontal disease.